Chest
Recent Advances in Chest MedicineRecent Advances in Dyspnea
Section snippets
Clinical Impact
Among 2, 258 patients with severe COPD (postbronchodilator FEV1 < 50% predicted), breathlessness was most problematic upon awakening in the morning.1 A majority of these patients reported daily and/or weekly variability in their breathing difficulty. Treatment with one long-acting bronchodilator was associated with less variability during the day.1 Women generally report more breathlessness than men.2 Pregnancy and menopause are important life events in women that are often associated with
Neurobiology of Dyspnea
A neurobiologic model that involves the respiratory and nervous systems has been used to describe our understanding of the perception of dyspnea18, 19, 20 (Fig 1). The respiratory system is modulated continuously by excitatory and inhibitory neuropeptides that act from sensory neurons to central networks.19 Endogenous opioids are inhibitory neuropeptides that affect respiratory rhythm and nociception. Studies have demonstrated that these substances modulate breathlessness in patients with COPD.
Exercise Testing to Investigate Dyspnea
Controversy has existed concerning the optimal exercise modality (treadmill vs cycle ergometer) to evaluate the intensity of dyspnea in the laboratory. Recent studies have confirmed that when the increase in work rate is matched between these two modalities, dyspnea ratings are similar for any level of ventilation.27, 28 Thus, either modality can be used as a stimulus to assess dyspnea.
The rise in dyspnea intensity during exercise in COPD is more closely linked to the decrease in dynamic
Measurement of Dyspnea
In a 2012 update, the American Thoracic Society proposed that dyspnea be considered across three different constructs: sensory, affective, and symptom impact or burden (Table 1).20 Generally, the intensity (sensory) and distress (affective) are considered in response to a specific stimulus, such as an exercise test or RLB, whereas the impact of dyspnea on an individual's daily activities may be considered in patient care or in a clinical trial.
Most instruments currently used to quantify
Dyspnea to Categorize Disease Severity
The GOLD (Global Initiative for Chronic Obstructive Lung Disease) committee recommended that symptom scores be used as one dimension to categorize the severity of COPD.37 Scores of 0-1 and 2-4 on the modified Medical Research Council (mMRC) scale differentiated those with less and more dyspnea, respectively.37 In a 2014 update, the GOLD committee revised this recommendation and prioritized that a comprehensive symptom assessment be used, including the COPD Assessment Tool and the Clinical COPD
Dyspnea as a Treatment Outcome
As breathing difficulty is the primary reason that most patients with cardiorespiratory disease seek medical care, it is reasonable to expect that relief of dyspnea would be a major treatment goal. The GOLD committee has recommended a treatment paradigm based on the severity of breathlessness on the mMRC scale.37 For example, different therapies are recommended for those patients with less dyspnea (mMRC = 0-1) and those with more dyspnea (mMRC = 2-4). The Canadian40 and Spanish41 COPD
Inhaled Medications in COPD
Bronchodilators reduce airway smooth muscle tone, improve airflow, and deflate the overinflated lung. Both classes of bronchodilators (as single agents) have consistently increased the resting IC in patients with COPD by an average of about 200 mL, or about 15%, from baseline. The improvement in IC is more pronounced in patients with resting lung hyperinflation. Changes of this magnitude have generally been associated with improvements in dyspnea and exercise endurance time.32
Randomized
Therapies in Idiopathic Pulmonary Fibrosis
Swigris and Fairclough68 proposed the use of the baseline and transition dyspnea indexes and the UCSD SOBQ to quantify patient-reported dyspnea in clinical trials involving patients with idiopathic pulmonary fibrosis (IPF). In two prospective studies involving patients with IPF, there was no beneficial treatment effect for dyspnea ratings on the TDI between bosentan and placebo over 1 year.69, 70 In a phase 3 trial in patients with IPF, King and colleagues71 reported no significant difference
Pulmonary Rehabilitation
Wadell and colleagues72 reported clinically meaningful improvements in the affective dimension (breathing-related anxiety) and symptom impact (TDI) of dyspneaafter 8 weeks of pulmonary rehabilitation compared with usual care in patients with COPD. They did not report clinically meaningful improvements in the sensory (intensity) domain.
Opioids
Opioids modulate the perception of dyspnea by decreasing respiratory drive (and associated corollary discharge), altering central perception, and/or decreasing anxiety.73 Fear of overdosing and the development of respiratory depression have historically limited the use of opioids for relieving dyspnea in clinical practice. However, recent statements by the American College of Chest Physicians (CHEST),74 the Canadian Thoracic Society,75 and the American Thoracic Society20 advocate that oral and
Novel Investigational Therapies
Novel treatments have been proposed for relief of dyspnea.84 Although each is based on a scientific rationale, supporting evidence from randomized clinical trials for these novel therapies is minimal and/or inconsistent. Consequently, these therapies are considered investigational at the present time.
Conclusions
Recent advances have expanded our understanding of the neurobiology of dyspnea. Laboratory investigations have demonstrated the role of endogenous opioids in modulating the perception of dyspnea in patients with COPD. Neuroimaging techniques have identified brain activity in the cortical-limbic network in healthy subjects when breathing discomfort/difficulty is provoked by a specific respiratory stimulus. Awareness of the different constructs of dyspnea has been a major advance that can be
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Mahler serves as a consultant to Boehringer Ingelheim GmbH, Forest Laboratories Inc, GlaxoSmithKline plc, Novartis AG, and Sunovion and serves on advisory boards of Forest Laboratories Inc, GlaxoSmithKline Plc, Merck & Co Inc, Novartis AG, Pearl Therapeutics Inc, and Sunovion Pharmaceuticals Inc. The Clinical Trials Office at Dartmouth-Hitchcock Medical Center has received grant
References (95)
- et al.
Understanding dyspnea as a complex individual experience
Maturitas
(2013) - et al.
Body mass index is related to the perception of exertional breathlessness in patients presenting with dyspnoea of unknown origin
Int J Cardiol
(2012) - et al.
Patients with COPD with higher levels of anxiety are more physically active
Chest
(2013) - et al.
Bidirectional associations between clinically relevant depression or anxiety and COPD: a systematic review and meta-analysis
Chest
(2013) - et al.
The impact of anxiety on the neural processing of respiratory sensations
Neuroimage
(2011) - et al.
Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD
Chest
(2002) - et al.
Meta-analysis of prognostic implications of dyspnea versus chest pain in patients referred for stress testing
Am J Cardiol
(2014) Dyspnea: a strong independent factor for long-term mortality in the elderly
J Nutr Health Aging
(2013)- et al.
Mechanisms of activity-related dyspnea in pulmonary diseases
Respir Physiol Neurobiol
(2009) - et al.
Effect of increased blood levels of β-endorphin on perception of breathlessness
Chest
(2013)
Antagonism of substance P and perception of breathlessness in patients with chronic obstructive pulmonary disease
Respir Physiol Neurobiol
Dyspnoea and the brain
Respir Med
Effect of modality on cardiopulmonary exercise testing in male and female COPD patients
Respir Physiol Neurobiol
Decline of resting inspiratory capacity in COPD: the impact on breathing pattern, dyspnea, and ventilatory capacity during exercise
Chest
Reliability and validity of the multidimensional dyspnea profile
Chest
GOLD 2011 disease severity classification in COPDGene: a prospective cohort study
Lancet Respir Med
American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association
J Am Coll Cardiol
American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
J Am Coll Cardiol
Effect of QVA149 on lung volumes and exercise tolerance in COPD patients: the BRIGHT study
Respir Med
Aclidinium bromide improves exercise endurance and lung hyperinflation in patients with moderate to severe COPD
Respir Med
Budesonide added to formoterol contributes to improved exercise tolerance in patients with COPD
Respir Med
INABLE 1 study group Effect of indacaterol on exercise endurance and lung hyperinflation in COPD
Respir Med
Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPD
Respir Med
Once-daily umeclidinium/vilanterol 125/25 mcg in COPD: a randomized, controlled study
Chest
A randomised trial of fluticasone furoate/vilanterol (50/25 μg; 100/25 μg) on lung function in COPD
Respir Med
Fluticasone furoate/vilanterol (100/25; 200/25 μg) improves lung function in COPD: a randomised trial
Respir Med
Patient-reported outcomes in idiopathic pulmonary fibrosis research
Chest
American College of Chest Physicians consensus statement on the management of dyspnea in patients with advanced lung or heart disease
Chest
Inhaled fentanyl citrate improves exercise endurance during high-intensity constant work rate cycle exercise in chronic obstructive pulmonary disease
J Pain Symptom Manage
Once-daily opioids for chronic dyspnea: a dose increment and pharmacovigilance study
J Pain Symptom Manage
Neuromuscular electrical stimulation improves clinical and physiological function in COPD patients
Respir Med
Symptom variability in patients with severe COPD: a pan-European cross-sectional study
Eur Respir J
Aging and sex differences
Women's mid-life health experiences in urban UK: an international comparison
Climacteric
Relationship of obesity with respiratory symptoms and decreased functional capacity in adults without established COPD
Prim Care Respir J
Pregnancy/obesity
When obesity and chronic obstructive pulmonary disease collide. Physiological and clinical consequences
Ann Am Thorac Soc
Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study investigators Determinants of depression in the ECLIPSE chronic obstructive pulmonary disease cohort
Am J Respir Crit Care Med
Depression and anxiety in chronic heart failure and chronic obstructive pulmonary disease: prevalence, relevance, clinical implications and management principles
Int J Geriatr Psychiatry
Anxiety, depression, and panic
Dyspnea: mechanisms, measurement, and management
American Thoracic Society Committee on Dyspnea An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea
Am J Respir Crit Care Med
Neuromodulatory effect of endogenous opioids on the intensity and unpleasantness of breathlessness during resistive load breathing in COPD
COPD
Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD
Eur Respir J
Dyspnea: mechanisms, measurement, and management
Does exercise test modality influence dyspnoea perception in obese patients with COPD?
Eur Respir J
Does dynamic hyperinflation contribute to dyspnoea during exercise in patients with COPD?
Eur Respir J
Cited by (101)
Cardiopulmonary exercise testing applied to respiratory medicine: Myths and facts
2023, Respiratory MedicineExperience of traditional East Asian medicine treatment in patients with chronic obstructive pulmonary disease: A qualitative study protocol
2023, European Journal of Integrative MedicineMXene/MWCNT electronic fabric with enhanced mechanical robustness on humidity sensing for real-time respiration monitoring
2022, Sensors and Actuators B: ChemicalCritical roles for breathing in the genesis and modulation of emotional states
2022, Handbook of Clinical NeurologyThe role of cardiopulmonary exercise testing in evaluating children with exercise induced dyspnoea
2021, Paediatric Respiratory Reviews
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.